There are three main ways that hormone therapy is used to treat hormone-sensitive breast cancer:
Adjuvant therapy for early-stage breast cancer: Tamoxifen is FDA approved for adjuvant hormone treatment of premenopausal and postmenopausal women (and men) with ER-positive early-stage breast cancer, and the aromatase inhibitors anastrozole, letrozole, and exemestane are approved for this use in postmenopausal women.
Research has shown that women who receive at least 5 years of adjuvant therapy with tamoxifen after having surgery for early-stage ER-positive breast cancer have reduced risks of breast cancer recurrence, including a new breast cancer in the other breast, and reduced risk of death at 15 years.
Until recently, most women who received adjuvant hormone therapy to reduce the chance of a breast cancer recurrence took tamoxifen every day for 5 years. However, with the introduction of newer hormone therapies (i.e., the aromatase inhibitors), some of which have been compared with tamoxifen in clinical trials, additional approaches to hormone therapy have become common.
For example, some women may take an aromatase inhibitor, instead of tamoxifen, every day for 5 years. Other women may receive additional treatment with an aromatase inhibitor after 5 years of tamoxifen. Finally, some women may switch to an aromatase inhibitor after 2 or 3 years of tamoxifen, for a total of 5 or more years of hormone therapy. Research has shown that for postmenopausal women who have been treated for early-stage breast cancer, adjuvant therapy with an aromatase inhibitor reduces the risk of recurrence and improves overall survival, compared with adjuvant tamoxifen.
Some premenopausal women with early-stage ER-positive breast cancer may have ovarian suppression plus an aromatase inhibitor, which was found to have higher rates of freedom from recurrence than ovarian suppression plus tamoxifen or tamoxifen alone.
Men with early-stage ER-positive breast cancer who receive adjuvant therapy are usually treated first with tamoxifen. Those treated with an aromatase inhibitor usually also take a GnRH agonist.
Decisions about the type and duration of adjuvant hormone therapy are complicated and must be made on an individual basis in consultation with an oncologist.
Treatment of advanced or metastatic breast cancer: Several types of hormone therapy are approved to treat metastatic or recurrent hormone-sensitive breast cancer. Hormone therapy is also a treatment option for ER-positive breast cancer that has come back in the breast, chest wall, or nearby lymph nodes after treatment (also called a locoregional recurrence).
Two SERMs, tamoxifen and toremifene, are approved to treat metastatic breast cancer. The antiestrogen fulvestrant is approved for postmenopausal women with metastatic ER-positive breast cancer that has spread after treatment with other antiestrogens. Fulvestrant is also approved for postmenopausal women with HR-positive, HER2-negative locally advanced or metastatic breast cancer who have not previously been treated with hormone therapy. In addition, it may be used in premenopausal women who have had ovarian ablation.
The aromatase inhibitors anastrozole and letrozole are approved to be given to postmenopausal women as initial therapy for metastatic or locally advanced hormone-sensitive breast cancer. Both of these drugs and the aromatase inhibitor exemestane are also approved to treat postmenopausal women with advanced breast cancer whose disease has worsened after treatment with tamoxifen. Men with advanced breast cancer who are treated with an aromatase inhibitor also receive a GnRH agonist.
Some women with advanced breast cancer are treated with a combination of hormone therapy and one of several targeted therapies:
- Palbociclib (Ibrance), is approved for use in combination with letrozole as initial therapy for the treatment of HR-positive, HER2-negative advanced or metastatic breast cancer in postmenopausal women. Palbociclib inhibits two cyclin-dependent kinases (CDK4 and CDK6) that appear to promote the growth of hormone receptor–positive breast cancer cells.
Palbociclib is also approved to be used in combination with fulvestrant for the treatment of postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer whose cancer has gotten worse after treatment with another hormone therapy. - Abemaciclib (Verzenio), another CDK4 and CDK6 inhibitor, is approved to be used in combination with fulvestrant for postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer whose disease has progressed after treatment with hormone therapy.
Abemaciclib is also approved to be used alone for women and men with HR-positive, HER2-negative advanced or metastatic breast cancer whose disease got worse after treatment with hormone therapy and previous chemotherapy given for metastatic disease.
Abemaciclib is also approved to be used with an aromatase inhibitor as first-line hormone therapy in postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer. - Ribociclib (Kisqali), another CDK4/6 inhibitor, is approved to be used in combination with an aromatase inhibitor in postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer that has not been treated with hormone therapy.
Ribociclib is also approved to be used in combination with fulvestrant in postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer who have not been treated with hormone therapy or whose disease got worse during treatment with hormone therapy. - Lapatinib (Tykerb) is approved to be used in combination with letrozole to treat hormone receptor–positive, HER2-positive metastatic breast cancer in postmenopausal women for whom hormone therapy is indicated. It is a small-molecule inhibitor of the HER2 and EGFR tyrosine kinases.
- Alpelisib (Piqray) is approved to treat breast cancer that is HR positive and HER2 negative and has a mutation in the PIK3CA gene. It is used with fulvestrant to treat postmenopausal women, and men, whose breast cancer is advanced or metastatic and has gotten worse during or after treatment with hormone therapy.
- Some women with advanced breast cancer that is HER2 and HR positive may receive hormone therapy plus trastuzumab with or without pertuzumab.
Neoadjuvant treatment of breast cancer: The use of hormone therapy to treat breast cancer to reduce tumor size before surgery (neoadjuvant therapy) has been studied in clinical trials. These trials have shown that neoadjuvant hormone therapy—in particular, with aromatase inhibitors—can be effective in reducing the size of breast tumors in postmenopausal women, but it is not yet clear how effective it is in premenopausal women.
Hormone therapy is sometimes used for the neoadjuvant treatment of HR-positive breast cancer in postmenopausal women who cannot tolerate chemotherapy or when surgery needs to be delayed.